The sub was refitted as part of a £5bn contract
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HMS Vanguard, the first of the navy's nuclear-powered Trident missile submarines to be refitted at a Devon dockyard, leaves Plymouth on Thursday.
HMS Vanguard arrived in Plymouth for refit two years ago. A dedicated dock was built at Devonport Dockyard to do the work as part of a £5bn contract.
During her time in Devonport, Vanguard has been the subject of a number of protests by anti-nuclear campaigners.
The submarine will now travel to her home port of Faslane in Scotland.
Special dock
HMS Vanguard was the first of four nuclear submarines which will be refitted at Devonport over the next seven years.
The 16,000-tonne subs, which form the backbone of the nation's nuclear deterrent, are berthed in specially-converted 9 dock because they are too big for the other docks.
HMS Vanguard will now undergo tests and sea trials before returning to service next year.